This is an application for a Mentored Patient-Oriented Research Career Development Award with a focus on developing expertise in the study of mindfulness meditation for the treatment of Generalized Anxiety Disorder (GAD), in addition to identifying neuroendocrine and neurocognitive changes associated with mindfulness meditation. GAD involves preoccupying worry, insomnia, irritability and poor concentration, and can lead to significant impairment in social and occupational functioning. Current therapies have limited effectiveness. Because the nature of the anxiety symptoms involve avoiding one's immediate experience, mindfulness meditation appears particularly suitable as a treatment for this disorder. Mindfulness meditation has already been shown to be helpful for several different health issues, but little data exists for anxiety disorders. To our knowledge, the protocol detailed here would be the first systematic controlled examination of mindfulness meditation in GAD. In addition, we propose to test neurocognitive and neuroendocrine changes in meditation which may provide valuable information regarding the mechanism of action of meditation. Because meditation involves being aware of present-moment reality, it may help correct the cognitive biases found in anxious individuals. Patients with GAD have a cognitive bias towards threat: they pay more attention to threatening; words and faces and interpret ambiguous stimuli as threatening. We hypothesize that MBSR training will > decrease this bias towards threat, and that this decrease will be associated with increases in the pro-approach pro-trust neuropeptide oxytocin. Oxytocin increases trust in humans and increases approach behavior to novel stimuli and reduces anxiety in a variety of animal species. Meditation also affects processes that are altered by the acute stress response, such as blood pressure and the stress hormone cortisol. We hypothesize that. mindfulness mediation, in the form of mindfulness-based stress reduction (MBSR) training, will reduce anxiety in individuals with GAD, and that this effect will be associated with decreases in the stress hormone cortisol. The proposed study will be conducted at the Massachusetts General Hospital and will complement a program of training and supervised research under the mentorship of Dr. Mark Pollack, with consultation from local and national experts. The career development program will emphasize skills necessary for designing and carrying out studies evaluating the efficacy and mechanism of meditation. This development plan includes a rich didactic component combining formal coursework at the Harvard School of Public Health on research methodology and statistics, as well as supervision with consultants in prospective study data design, statistical analysis and neuroendocrine physiology and pathophysiology, that will lay the foundation for future independent investigation by the candidate in this area. [unreadable] [unreadable] [unreadable]